An Efficient and Simple Procedure for the Preparation of α-Keto-β-lactams

Abstract

585α-Keto-β-lactams 1 are at the crossroads of many important transformations leading to bioactive compounds [1]. Recently, we used yeast-catalyzed reduction of 1-(4-methoxyphenyl)-4-phenyl-2,3-azetidindione as a key step in a biocatalytic approach to the synthesis of the paclitaxel C-13 side chain (Scheme 1) [2]. To investigate other 4-substituted α-keto-β-lactams as substrates for microbial reductions and subsequent conversions to optically pure C-13 side-chain analogs we required a simple, efficient, and general protocol for the synthesis of these compounds.Abstract. The methods for the preparation of α-keto-β-lactams described in the literature are generally specific for a particular target molecule and lack generality. A short route to several of these compounds has been developed and is deods, therefore, are suitable only for the preparation of compounds with acid-resistant substituents. Thus, low reactivity of the quaternary center in the intermediates A, B, or C (the latter accessible via cyclization of a thio-precursor followed by chlorination) towards nucleophilic attack limits the applicability of these otherwise simple and straightforward syntheses.scribed in this communication. The protocol based on an efficient cyclization procedure followed by hydrolysis and oxidation allows preparation of α-keto-β-lactams 5a -g with sensitive substituents.

Novel and Recent Synthesis and Applications of β-Lactams

“…A protocol has been reported based on a cyclization procedure followed by hydrolysis and oxidation, which allowed the preparation of a-keto-b-lactams (Scheme 11), [59]. The cyclization of imines with acetylglyoxylic acid, in the presence of POCl 3 and Et 3 N, gave 3-acetoxy-b-lactams in good yields as cisisomers, prevalently.…”

One-Pot Construction of Diverse β-Lactam Scaffolds via the Green Oxidation of Amines and Its Application to the Diastereoselective Synthesis of β-Amino Acids

“…Yellow oil, 321.0 mg, 65%; 1 H NMR (400 MHz, CDCl 3 ): δ 7.28 (t, J = 8.0 Hz, 1H), 7.20 (t, J = 7.7 Hz, 1H), 6.90− 6.87 (m, 2H), 6.82−6.79 (m, 2H), 6.71 (d, J = 7.7 Hz, 1H), 6.66 (t, J = 1.8 Hz, 1H), 4.78 (d, J = 14.5 Hz, 1H), 4.66 (d, J = 4.1 Hz, 1H), 4.56 (d, J = 4.1 Hz, 1H), 3.83 (d, J = 15.0 Hz, 1H), 3.78 (s, 3H), 3.75 (s, 3H), 3.13 (s, 3H); 13 (±)-cis-1-Benzyl-2-oxo-4-phenylazetidin-3-yl acetate (5i). 58 Colorless oil, 242.1 mg, 55%; 1 H NMR (400 MHz, CDCl (±)-cis-1-Benzyl-3-phenoxy-4-phenylazetidin-2-one (5j). 48 White solid, 209.0 mg, 42%; 1 H NMR (400 MHz, CDCl 3 ): δ 7.33−7.26 (m, 8H), 7.17 2, 5a).…”

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

“…The spectral data are in accordance with those reported in the literature. 70 Enzyme Production and Purification. The genes for mutant R134A of the T. thermosaccharolyticum sucrose 6′phosphate phosphorylase (TtSPP_R134A; UniProt ID D9TT09), the A. caldus sucrose synthase (SuSy; UniProt ID A0A059ZV61) and the S. rebaudiana UDP-glucosyltransferase (UGT-76G1Sr; UniProt ID Q6VAB4) were ligated into expression vectors, transformed in Escherichia coli and expressed recombinantly as described in earlier work.…”